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Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients.
Maifeld, A, Bartolomaeus, H, Löber, U, Avery, EG, Steckhan, N, Markó, L, Wilck, N, Hamad, I, Šušnjar, U, Mähler, A, et al
Nature communications. 2021;(1):1970
Abstract
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
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Gut microbiota associations with metabolic syndrome and relevance of its study in pediatric subjects.
Carrizales-Sánchez, AK, García-Cayuela, T, Hernández-Brenes, C, Senés-Guerrero, C
Gut microbes. 2021;(1):1960135
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Abstract
Childhood obesity and T2DM have shown a recent alarming increase due to important changes in global lifestyle and dietary habits, highlighting the need for urgent and novel solutions to improve global public health. Gut microbiota has been shown to be relevant in human health and its dysbiosis has been associated with MetS, a health condition linked to the onset of relevant diseases including T2DM. Even though there have been recent improvements in the understanding of gut microbiota-host interactions, pediatric gut microbiota has been poorly studied compared to adults. This review provides an overview of MetS and its relevance in school-age children, discusses gut microbiota and its possible association with this metabolic condition including relevant emerging gut microbiome-based interventions for its prevention and treatment, and outlines future challenges and perspectives in preventing microbiota dysbiosis from the early stages of life.
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Dysbiosis of the intestinal microbiome as a component of pathophysiology in the inborn errors of metabolism.
Kirby, TO, Ochoa-Reparaz, J, Roullet, JB, Gibson, KM
Molecular genetics and metabolism. 2021;(1):1-10
Abstract
Inborn errors of metabolism (IEMs) represent monogenic disorders in which specific enzyme deficiencies, or a group of enzyme deficiencies (e.g., peroxisomal biogenesis disorders) result in either toxic accumulation of metabolic intermediates or deficiency in the production of key end-products (e.g., low cholesterol in Smith-Lemli-Opitz syndrome (Gedam et al., 2012 [1]); low creatine in guanidinoacetic acid methyltransferase deficiency (Stromberger, 2003 [2])). Some IEMs can be effectively treated by dietary restrictions (e.g., phenylketonuria (PKU), maple syrup urine disease (MSUD)), and/or dietary intervention to remove offending compounds (e.g., acylcarnitine excretion with the oral intake of l-carnitine in the disorders of fatty acid oxidation). While the IEMs are predominantly monogenic disorders, their phenotypic presentation is complex and pleiotropic, impacting multiple physiological systems (hepatic and neurological function, renal and musculoskeletal impairment, cardiovascular and pulmonary activity, etc.). The metabolic dysfunction induced by the IEMs, as well as the dietary interventions used to treat them, are predicted to impact the gut microbiome in patients, and it is highly likely that microbiome dysbiosis leads to further exacerbation of the clinical phenotype. That said, only recently has the gut microbiome been considered as a potential pathomechanistic consideration in the IEMs. In this review, we overview the function of the gut-brain axis, the crosstalk between these compartments, and the expanding reports of dysbiosis in the IEMs recently reported. The potential use of pre- and probiotics to improve clinical outcomes in IEMs is also highlighted.
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Dietary Fibre Modulates the Gut Microbiota.
Cronin, P, Joyce, SA, O'Toole, PW, O'Connor, EM
Nutrients. 2021;(5)
Abstract
Dietary fibre has long been established as a nutritionally important, health-promoting food ingredient. Modern dietary practices have seen a significant reduction in fibre consumption compared with ancestral habits. This is related to the emergence of low-fibre "Western diets" associated with industrialised nations, and is linked to an increased prevalence of gut diseases such as inflammatory bowel disease, obesity, type II diabetes mellitus and metabolic syndrome. The characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as high plasma cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Gut microbial signatures are also altered significantly in these cohorts, suggesting a causative link between diet, microbes and disease. Dietary fibre consumption has been hypothesised to reverse these changes through microbial fermentation and the subsequent production of short-chain fatty acids (SCFA), which improves glucose and lipid parameters in individuals who harbour diseases associated with dysfunctional metabolism. This review article examines how different types of dietary fibre can differentially alter glucose and lipid metabolism through changes in gut microbiota composition and function.
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The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases.
Hosseinkhani, F, Heinken, A, Thiele, I, Lindenburg, PW, Harms, AC, Hankemeier, T
Gut microbes. 2021;(1):1-22
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Abstract
The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, and autoimmune disease. The majority of these altered interactions arise through metabolic cross-talk between gut microbiota and host immune system, inducing a low-grade chronic inflammation that characterizes all NCDs. In this review, we discuss the contribution of bacterial metabolites to immune signaling pathways involved in NCDs. We then review recent advances that aid to rationally design microbial therapeutics. A deeper understanding of these intersections between host and gut microbiota metabolism using metabolomics-based system biology platform promises to reveal the fundamental mechanisms that drive metabolic predispositions to disease and suggest new avenues to use microbial therapeutic opportunities for NCDs treatment and prevention. Abbreviations: NCDs: non-communicable disease, IBD: inflammatory bowel disease, IL: interleukin, T2D: type 2 diabetes, SCFAs: short-chain fatty acids, HDAC histone deacetylases, GPCR G-protein coupled receptors, 5-HT: 5-hydroxytryptamine receptor signaling, DCs: dendritic cells, IECs: intestinal epithelial cells, T-reg: T regulatory cell, NF-κB: nuclear factor κB, TNF-α: tumor necrosis factor alpha, Th: T helper cell, CNS: central nervous system, ECs: enterochromaffin cells, NSAIDs: non-steroidal anti-inflammatory drugs, AhR: aryl hydrocarbon receptor, IDO: indoleamine 2,3-dioxygenase, QUIN quinolinic acid, PC: phosphatidylcholine, TMA: trimethylamine, TMAO trimethylamine N-oxide, CVD: cardiovascular disease, NASH nonalcoholic steatohepatitis, BAs: bile acids, FXR: farnesoid X receptor, CDCA chenodeoxycholic acid, DCA: deoxycholic acid, LCA: lithocholic acid, UDCA ursodeoxycholic acid, CB: cannabinoid receptor, COBRA constraint-based reconstruction and analysis.
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Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis.
Person, H, Keefer, L
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110209
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Abstract
The high comorbidity of psychological disorders in both functional and organic gastrointestinal diseases suggests the intimate and complex link between the brain and the gut. Termed the brain-gut axis, this bidirectional communication between the central nervous system and enteric nervous system relies on immune, endocrine, neural, and metabolic pathways. There is increasing evidence that the gut microbiome is a key part of this system, and dysregulation of the brain-gut-microbiome axis (BGMA) has been implicated in disorders of brain-gut interaction, including irritable bowel syndrome, and in neuropsychiatric disorders, including depression, Alzheimer's disease, and autism spectrum disorder. Further, alterations in the gut microbiome have been implicated in the pathogenesis of organic gastrointestinal diseases, including inflammatory bowel disease. The BGMA is an attractive therapeutic target, as using prebiotics, probiotics, or postbiotics to modify the gut microbiome or mimic gut microbial signals could provide novel treatment options to address these debilitating diseases. However, despite significant advancements in our understanding of the BGMA, clinical data is lacking. In this article, we will review current understanding of the comorbidity of gastrointestinal diseases and psychological disorders. We will also review the current evidence supporting the key role of the BGMA in this pathology. Finally, we will discuss the clinical implications of the BGMA in the evaluation and management of psychological and gastrointestinal disorders.
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Gut microbes and health.
Álvarez, J, Fernández Real, JM, Guarner, F, Gueimonde, M, Rodríguez, JM, Saenz de Pipaon, M, Sanz, Y
Gastroenterologia y hepatologia. 2021;(7):519-535
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Abstract
The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.
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Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).
Ratajczak, W, Mizerski, A, Rył, A, Słojewski, M, Sipak, O, Piasecka, M, Laszczyńska, M
Aging. 2021;(8):10934-10954
Abstract
Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.
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Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors.
Galié, S, García-Gavilán, J, Camacho-Barcía, L, Atzeni, A, Muralidharan, J, Papandreou, C, Arcelin, P, Palau-Galindo, A, Garcia, D, Basora, J, et al
Molecular nutrition & food research. 2021;(19):e2000982
Abstract
SCOPE To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day-1 ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.
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Beneficial Effects of Phenolic Compounds on Gut Microbiota and Metabolic Syndrome.
Kasprzak-Drozd, K, Oniszczuk, T, Stasiak, M, Oniszczuk, A
International journal of molecular sciences. 2021;(7)
Abstract
The human intestine contains an intricate community of microorganisms, referred to as the gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, medicines and environmental factors, particularly diet. Growing evidence supports the involvement of GM dysbiosis in gastrointestinal (GI) and extraintestinal metabolic diseases. The beneficial effects of dietary polyphenols in preventing metabolic diseases have been subjected to intense investigation over the last twenty years. As our understanding of the role of the gut microbiota advances and our knowledge of the antioxidant and anti-inflammatory functions of polyphenols accumulates, there emerges a need to examine the prebiotic role of dietary polyphenols. This review firstly overviews the importance of the GM in health and disease and then reviews the role of dietary polyphenols on the modulation of the gut microbiota, their metabolites and how they impact on host health benefits. Inter-dependence between the gut microbiota and polyphenol metabolites and the vital balance between the two in maintaining the host gut homeostasis are also discussed.